E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the antihypertensive effects of a once daily fixed oral dose of CHF 1521 (delapril 30 mg and manidipine 10 mg, in combination), compared with once daily losartan 50 mg and hydrochlorothiazide 12.5 mg in combination, over a twelve-week period, assessed by 24-h ambulatory blood pressure monitoring, in type 2 diabetic patients with mild to moderate essential hypertension . |
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E.2.2 | Secondary objectives of the trial |
To investigate the tolerability of a once daily fixed oral dose of CHF 1521 (delapril 30 mg and manidipine 10 mg, in combination), compared with once daily losartan 50 mg and hydrochlorothiazide 12,5 mg in combination, over a twelve-week period, in type 2 diabetic patients with mild to moderate essential hypertension. To investigate the effects on glicemia and glycosilate haemoglobin of a once daily fixed oral dose of CHF 1521 compared with once daily losartan 50 mg and hydrochlorothiazide 12,5 mg in combination, over a twelve-week period, in type 2 diabetic patients with mild to moderate essential hypertension. To investigate the effects on microalbuminuria (microalbuminuria sub-study) of a once daily fixed oral dose of CHF 1521 compared with once daily losartan 50 mg and hydrochlorothiazide 12,5 mg in combination, over a twelve-months period, in a subgroup of 120 type 2 diabetic patients with mild to moderate essential hypertension and with microalbuminuria at the inclusion.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
To be included in this study, patients must satisfy the following criteria at the time points specified: At Visit 1 (Day -7): Male or female > 45 years (females of child bearing potential must be using adequate contraceptive precautions) Females of childbearing potential or within two years of the menopause must have a negative urine pregnancy test at enrolment visit Patients are attending an out-patient clinic visit Type 2 diabetes controlled by diet and oral antidiabetic treatment (HbA1c < 7.5%). Patients with mild to moderate uncomplicated essential hypertension with a trough mean sitting DBP 85 and 105 mmHg and SBP <160 mmHg No evidence of significant cardiovascular disease other than hypertension in the opinion of the investigator Written informed consent Agreement to attend all study visits as planned in the protocol Presence of persistent microalbuminuria (presence of urinary albumin-creatinine ratio: 2.5-25 mg/mmol for men and 3.5-25 mg/mmol for women, confirmed by at least one previous test in the last 3 months) for the patients to be included in the microalbuminuria sub-study.
At Visit 2 (Day 0): Mild to moderate hypertension, defined as a trough mean sitting DBP > 85 and < 105 mmHg and SBP <160 mmHg 24-hour mean SBP > 130 mmHg (as measured by ABPM) For the patients of the Microalbuminuria sub-study, presence of microalbuminuria (urinary albumin-creatinine ratio: 2.5-25 mg/mmol for men and 3.5-25 mg/mmol for women)
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if one or more of the following statements are applicable at enrolment visit: In the investigator’s opinion the patient should not be withdrawn from their current antihypertensive medication Malignant or secondary hypertension (e.g. patients with hyperaldosteronism, pheochromocytoma, renal artery stenosis, renal parenchymal disease, coarctation of the aorta, Cushing’s disease syndrome) History of severe elevated blood pressure (mean sitting DBP >110 mmHg and/or SBP >160 mmHg Orthostatic hypotension (difference between mean sitting and standing SBP >20 mmHg) Obesity as defined by a Body Mass Index (BMI) > 32 Kg/m2 Chronic glaucoma treated with beta-blocker eye drops Hypertensive retinopathy (Keith Wagener Barker [KWB] scale) grade 3 or 4 History of hypertensive encephalopathy or cerebrovascular accident Presence of cardiac disease other than: uncomplicated hypertensive cardiovascular disease or a single uncomplicated myocardial infarction (MI), which occurred a minimum of twelve months before this study with stable ECG findings for a minimum of twelve months before this study History of MI complicated by congestive heart failure or post-MI angina Presence of any conduction arrhythmia including bradycardia (heart rate <45 beats per minute (bpm)), tachycardia (heart rate >100 bpm), ventricular arrhythmia Presence of significant pulmonary, hepatic, renal, endocrine, metabolic or haematological disease, disorder, or dysfunction Laboratory evidence of significant disease including the following: serum creatinine >1.5 mg/dl serum potassium >10% x upper limit of normal (ULN) aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN and/or total serum bilirubin >1.5 x ULN Presence of gastrointestinal disease or history of gastrointestinal surgery which would interfere with drug absorption History of significant allergies (including multiple drug allergies) History of cancer including leukaemia and lymphoma within the past five years (skin cancer, other than melanoma, is an exception) Diabetes mellitus requiring treatment with insulin Uncontrolled diabetes (HbA1c > 7.5%) Chronic use of any drug known to affect blood pressure such as: tricyclic antidepressants, monoamine oxidase inhibitors, neuroleptic drugs (any type), centrally acting antihypertensives (e.g. clonidine, methyldopa, guanfacin, moxonidine), reserpin, non-steroidal anti-inflammatory drug (NSAID) (acetylsalicylic acid [ASA] <0.5 gram/day is allowed), oral or parenteral corticosteroids, antiarrhythmic drugs, digitalis and cardiac glycosides, amphetamine and its derivatives Concomitant treatment with other antihypertensive drugs different from the study drugs (i.e. alpha receptor blockers and agonists, beta receptor blockers and agonists, calcium antagonists ACE-inhibitors, angiotensin–II receptor antagonist and diuretics) Concomitant use of lithium salts Known allergy or a known intolerance to any calcium-antagonist or ACE-inhibitors or ARB or HCTZ. Females who are pregnant or lactating Use of any investigational drug within 28 days before visit 1 Patients previously enrolled into the study History of drug, medications abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy parameter of this study is the change from baseline to the end of the study (Day +84) in the 24-hour mean SBP, measured by ABPM. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |